This report describes studies on the biochemical and physiological mechanisms by which cell functions are regulated by hormones, agonists, and in pathophysiology 1 states, including aging. The presence of various Regulatory GTP-binding proteins that couple cell surface receptors to their effector systems were show the Kidney. Decreases in vitro transcription rates of mRNAs for Gs and Gi re observed during aging, but a decrease in level was seen only for Gs. Receptor mediated effects on cyclic AMP and phosphoinositide metabolism and on second messenger regulation of protein kinases were described in cultured kidney and bone cells. PTH regulation of protein kinase C was shown in renal cells, along with differential regulation of protein kinase A and C activity by PTH antagonist. Dopamine regulation of cyclic AMP production was shown for the first time in an established renal cell line. Purinergic regulation of cytosolic Ca2+ in bone cells was shown to result from increased phosphoinositide metabolism. without crosstalk from simultaneous changes in cyclic AMP metabolism Considerable heterogeneity was observed in Ca2+ metabolism of individual skin fibroblast from Alzheimer's disease patients and age-matched controls, precluding at present firm conclusions regarding purported differences. Ammoniagenesis in the renal proximal tubule, unlike that in brain, small intestine, and the glomerulus, is regulated by acidosis and glucocoricoids. Glomeruli ammoniagenesis was increased in old rats and associated with the degree of renal failure.